1. Field of the Invention
The present invention relates to cross-linked polymer microspheres.
2. Description of the Related Art
Mono- or narrow-dispersed cross-linked polymer microspheres have gained increasing attention due to their uniform packing, providing a uniform flow velocity profile and low back-pressure for high efficiency chromatography.
However, currently available cross-linked polystyrene microspheres have somewhat limited applications, mainly due to the absence of available functional groups at the surface. They also require surfactants which are costly and may contaminate the surface as well as multiple swelling steps during manufacture of porous microspheres, which complicates the process.
Efforts continue to simplify and better control the manufacturing process, and to overcome the effects of `coagulation` which is a chemical process known to be a primary cause of failure in the attempt of forming superior mono-disperse microspheres.
Coagulation is the process by which a droplet of an immiscible additive collects or coagulates with other droplets of the same additive to reduce the collective exposed surface area of the droplets to the medium. This phenomenon is commonly seen, for example, when oil droplets are added to water.
One conventional technique to form microspheres, known as suspension polymerization, utilizes a nonhomogeneous reaction mixture that involves a suspension of droplets in a immiscible liquid, such as water. In this case, the droplets themselves form individual polymerization reactors, with all the necessary components to form a single microsphere. However, this can occur only if the droplets are kept separate from one another during the final stages of polymerization. Coagulation during the final stages will adversely affect the dispersity characteristics of the resulting batch of microspheres (an `assemblage`) and perhaps the individual characteristics of the microspheres themselves.
Emulsion polymerization is able to provide mono-disperse cross-linked microspheres of up to about one micron diameter in a single step, or up to many microns in the so-called seeded swelling techniques, notably those pioneered by Ugelstad.
In a process known as dispersion copolymerization, the polymerization takes place in organic media and the strong tendency for microspheres to coagulate is reduced by the use of disperants (Li and Stover J. Polym. Sci., Polym. Chem., 31, 2473, 1993). However, in all of the above processes, including suspension, emulsion, seeded emulsion and dispersion polymerization, the surface of the microspheres is contaminated by dispersant residues and other stabilizers, potentially limiting their end uses.
A recent technique known as precipitation polymerization was published by Li and Stover J. Polym. Sci., Polym. Chem., 31, 3257 (1993), the subject matter of which is incorporated herein by reference. In this technique, the monomer is soluble in the polymerization medium while the polymer is insoluble and precipitates out of solution.
In contrast to the aforementioned dispersion copolymerization, this technique does not require the presence of any surfactants, dispersants or stabilizers whatsoever. However, the resulting microspheres, while mono-disperse and highly cross-linked still lack the necessary functional groups and porosity to broaden their end uses.
Narrow or mono-dispersed microspheres have gained particular favour as a separation medium in view of the massive surface areas that can be achieved by establishing a porous bulk structure or porous outer shell. The conventional method to prepare the porous styrene-type microspheres is by suspension polymerization of commercial divinylbenzene (DVB-55). Permanent porosity in the microspheres is created with the help of programs. However, microspheres prepared by suspension polymerization usually have broad particles size distributions, requiring size fractionation to remove the fine particles. Even after size fractionation, the microspheres are not mono-disperse, thus reducing their chromatography column efficiency and increasing the back pressure of the packed column.
Mono-dispersed, cross-linked, porous microspheres may be produced by seeded swelling techniques. However, this is a time consuming process, requiring the use of surfactants.
It is the object of the present invention to provide an improved precipitation polymerization technique to form both functional and porous microspheres.